[Renal transport and nephrotoxicity of cephaloridine (author's transl)].
Large doses of cephaloridine (CER) cause acute necrosis of the proximal renal tubule in various species, as well as gentamicin (GM). However, administration of the two drugs simultaneously resulted in a protective effect of CER against GM related nephrotoxicity in rats. The present studies were designed to examine the mechanism of CER transport system into renal cells in vitro, using the rat kidney slices and 3H-CER, effects of transport system of CER by GM or cephalexin, and effects on CO2 production in rat kidney slices of CER and GM. The results were as follows: 1. CER was transported into cells actively and intracellular concentration of CER became to be equal to extracellular concentration on around 100 mcg/ml of extracellular concentration of CER. 2. GM and CEX inhibited intracellular active transport of CER. 3. CER had inhibitory effect on CO2 production in rat kidney slices and its effect was dose dependent. GM had no effect on CO2 production. The author concluded that intracellular transport system of CER, GM and CEX is the same, and competition may be present, if each drugs are administrated simultaneously. Different attitude on CO2 production of CER and GM does not explain the difference of the mechanism of renal toxicity of each drugs directly. However, it may explain that the mechanism of renal toxicity of CER is not the same as of GM in parts.
D000818:Animals; D002245:Carbon Dioxide / Q000096:biosynthesis; D002506:Cephalexin / Q000494:pharmacology; D002509:Cephaloridine / Q000008:administration & dosage / Q000378:metabolism* / Q000633:toxicity; D004347:Drug Interactions; D005839:Gentamicins / Q000008:administration & dosage / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000187:drug effects*; D008297:Male; D051381:Rats
D005839:Gentamicins; D002245:Carbon Dioxide; D005947:Glucose; D002509:Cephaloridine; D002506:Cephalexin